Detection of Disease-Related Changes in Pre-Symptomatic Alzheimer's Disease (Scope)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Pfizer
Heidelberg Engineering, Inc.
Neurotrack
Optovue
Avid Pharmaceuticals
Information provided by (Responsible Party):
Rhode Island Hospital
ClinicalTrials.gov Identifier:
NCT01841905
First received: April 24, 2013
Last updated: January 18, 2016
Last verified: January 2016
  Purpose
The investigators are conducting a study to try to improve our ability to identify older adults who are at high-risk for progression to Alzheimer's disease, several years before they have symptoms that might reduce their quality of life. The investigators believe they can increase the sensitivity of tests of memory and problem solving, by using a very small dose of a medication (scopolamine) that reduces the activity of the principal chemical system in the brain that is changing in the earliest stages of Alzheimer's disease. By pairing this "micro-dose" drug challenge (that is administered with a tiny needle placed just under the surface of the skin on the forearm), with our tests of memory and thinking, it is believed that the investigators can create a "stress test" that is very similar in concept to the use of the exercise treadmill to make the results of a heart EKG more sensitive to detect early disease, as a cardiac stress test for heart disease. The investigators want to create a similar stress test for Alzheimer's disease (AD).

Condition Intervention
Alzheimer's Disease
Other: Observational Study

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Detection of Disease-Related Changes in Pre-Symptomatic Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by Rhode Island Hospital:

Primary Outcome Measures:
  • Groton Maze Learning Test [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
    Total number of correct moves over 5 trials on the Groton Maze Learning Test at 3 hours


Secondary Outcome Measures:
  • Groton Maze Learning Test [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
    Mean number of correct moves per second on the Groton Maze Learning Test at 3 hours

  • CogState One-Back Learning (OBK) Task [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
    Overall performance across study visits.

  • 12-Item International Shopping List Test - Immediate and Delayed Recall (CogState) [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
    Overall performance across study visits.

  • Rentz Face-Name Association Test [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
    Overall performance across study visits.

  • Stark Pattern Separation Test [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
    Overall performance across study visits.

  • Minnesota Cognitive Acuity Scale (MCAS) [ Time Frame: Pre-baseline ] [ Designated as safety issue: No ]
    Screening acuity.

  • Saliva Sample for DNA Analyses (ApoE and BDNF genotyping) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Mutation status.

  • Non-invasive imaging of macula, retinal function and visual fields [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
    Change over time.

  • CogState Once-Card learning (OCL) Task [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
    Overall performance across study visits.

  • Amyloid and Alzheimer's Psycho-educational Session [ Time Frame: 9 and 18 month study visits ] [ Designated as safety issue: No ]
    An informational exercise to provide further information about amyloid PET imaging and to determine the impact of this disclosure of study participants.

  • Tokyo Subway Navigation [ Time Frame: 9 month follow-up visit ] [ Designated as safety issue: No ]
    A functional activity of daily living where study participants are given pre-determined destinations / conditions and asked to map the route. Main outcome measure for this assessment is time taken to solve the problem.

  • MAC-Q [ Time Frame: Pre-screen, Baseline, 9 & 18 month follow-up ] [ Designated as safety issue: No ]
    A six-item scale measuring age-related memory decline. An overall index of cognitive decline is calculated by summing scores for all six items with double weighting for item #6. Higher scores indicate greater decline in memory.


Estimated Enrollment: 60
Study Start Date: July 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Observational Study
Pre-Symptomatic Alzheimers' Disease
Other: Observational Study
Observational Study

Detailed Description:

We will take pictures of subjects' brains using PET imaging, in healthy older adults (ages 55 to 80 years) who have both a family history of AD, and who have concerns about changes in their memory (but no clinical symptoms of AD), to see how much of a protein - that is related to AD -is in their brains. When all subjects come to the hospital for PET imaging, we will review the entire study plan with them, the risks and benefits of participation, and we will obtain written informed consent at that time. Our goal is to compare performance on our new stress test to these PET imaging results. Once the PET imaging is done, we will have each subject come to our clinical research unit for a day-long baseline visit. In the morning we will give the tests of memory and thinking, and then we will administer the injection of scopolamine at a very low dose. We will then continue to examine the subjects, and to give the memory and thinking tests at 1, 3, 5, 7, and 8 hours post-dosing. Once they have fully-recovered from all effects of the medication, they will be allowed to go home that day. We will then see all subjects again, for much shorter visits to complete the cognitive tests, at both 9 and 18 months after their initial study visit. We will follow all subjects for 18 months to see which of them show very mild but measurable changes on the memory and thinking tests, as we predict that these will be the same persons who also had stronger results on our stress test at the first study visit.

At all three study visits to our clinical research unit, we will obtain measurements using an imaging device that uses infrared and blue light to take picture of the eye and retina. Our secondary goal in this study to search for evidence of the same protein, in the retina, that builds up and is seen with PET imaging of the brain in persons who are at high risk for AD. Finally, we are also collecting a small sample of saliva, at the first visit to our unit, in order to see which subjects have a genetic risk for the disease, as this genetic risk may affect how we interpret the results of our new "cognitive stress test".

In this study, a small dose of an already approved medication (used to treat seasickness) will be used to temporarily, and safely, mimic signs of very early disease during just the first day of testing. This is a methodological study to determine if tests that measure how you think can predict the risk of dementia as we age.

  Eligibility

Ages Eligible for Study:   55 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Individuals between the ages of 55 and 80 years old, and who have two risk factors for AD (subjective memory complaints as ascertained on a standardized questionnaire and a positive family history for the disease).
Criteria

Inclusion Criteria:

  • Individuals between the ages of 55 and 80 years old (inclusive).
  • MMSE total score > 27
  • Two risk factors for AD:
  • Subjective memory complaints.
  • A positive (suspected) first-degree family history for the disease.
  • Permitted medications stable for at least 1 month prior to screening.
  • Subjects may take stable doses of antidepressants lacking significant anticholinergic side effects (do not have a history of major depression within the past year).
  • Estrogen replacement therapy.
  • Adequate visual and auditory acuity to allow neuropsychological testing.
  • Good general health or without any clinically significant abnormalities .
  • Vitamin supplements (including Vitamin E) will be acceptable.
  • Subjects must be willing and able to provide written informed consent.

Exclusion Criteria:

  • History of major traumatic brain injury, other known neurologic disease or insult
  • Mini Mental State Examination (MMSE)total score < 27
  • Regular (daily) use of narcotics or antipsychotic medications
  • Poorly-controlled major depression or another Axis I psychiatric disorder as described in DSM-IV within the past year.
  • Psychotic features, agitation or behavioral problems, within the last 3 months.
  • History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria).
  • History of schizophrenia (DSM IV criteria).
  • Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol including:
  • History of systemic cancer within the past 5 years (non-metastatic skin cancers are acceptable).
  • History of myocardial infarction in the past year or unstable or severe cardiovascular disease including angina or Congestive Heart Failure (CHF) with symptoms at rest.
  • Clinically significant obstructive pulmonary disease or asthma.
  • Clinically significant and unstable gastrointestinal disorder within two years.
  • Insulin-requiring diabetes or uncontrolled diabetes mellitus.
  • Uncontrolled hypertension (systolic BP > 170 or diastolic BP > 100).
  • History of clinically significant liver disease, coagulopathy, or vitamin K deficiency within the past 2 years.
  • History of symptoms of narrow-angle glaucoma.
  • Clinically significant obstructive uropathy
  • Use of centrally active beta-blockers, narcotics, methyldopa and clonidine within 4 weeks prior to screening.
  • Use of anti-Parkinsonian medications (e.g., Sinemet, amantadine, bromocriptine, pergolide and selegiline) within 2 months prior to screening.
  • Use of neuroleptics or narcotic analgesics within 4 weeks prior to screening.
  • Use of long-acting benzodiazepines or barbiturates within 4 weeks prior to screen.
  • Use of short-acting anxiolytics or sedative-hypnotics more frequently than 2 times per week within 4 weeks prior to screening (note: sedative agents should not be used within 72 hours of the baseline and follow-up visits.
  • Initiation or change in dose of an antidepressant lacking significant cholinergic side effects within the 4 weeks prior to screening (use of stable doses of antidepressants for at least 4 weeks prior to screening is acceptable)
  • Use of systemic corticosteroids within 3 months prior to screening.
  • Medications with significant cholinergic or anticholinergic side effects within 4 weeks prior to screening.
  • Use of anti-convulsants within 2 months prior to screening.
  • Use of warfarin (Coumadin) within 4 weeks prior to screening.
  • Any prior use of any FDA approved medications for the treatment of Alzheimer's disease (e.g., tacrine, donepezil, or other newly approved medications).
  • Use of any investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to screening.
  • Subjects who, in the investigator's opinion, will not comply with study procedures.
  • Known hypersensitivity to F-18, tropicamide, and/or scopolamine or agents of this class of drugs.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01841905

Locations
United States, Rhode Island
Lifespan
Providence, Rhode Island, United States, 02903
Sponsors and Collaborators
Rhode Island Hospital
Pfizer
Heidelberg Engineering, Inc.
Neurotrack
Optovue
Avid Pharmaceuticals
Investigators
Principal Investigator: Peter J. Snyder, Ph.D. Sr. Vice President & Chief Research Officer, Lifespan
  More Information

Responsible Party: Rhode Island Hospital
ClinicalTrials.gov Identifier: NCT01841905     History of Changes
Other Study ID Numbers: 900,421-477 
Study First Received: April 24, 2013
Last Updated: January 18, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Rhode Island Hospital:
Alzheimer's Disease
Family History
Memory Concerns

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 28, 2016